Innowave MTB/RIF/INH facilitates timely and accurate diagnosis of multiple-drug resistant tuberculosis as a near POCT technique: a multicenter prospective on-site performance evaluation study

Abstract Background Many rifampicin (RIF)-resistant (RR) tuberculosis (TB) patients remain sensitive to isoniazid (INH), which challenges the strategy of using RR as an instant indicator of multiple-drug resistance tuberculosis (MDR-TB). A molecular test capable of concurrently detecting RIF and INH resistance is urgently needed. Methods The performance of a novel rapid molecular test, Innowave MTB/RIF/INH (InnowaveDX) was evaluated prospectively in three tertiary hospitals. Its capability of detecting resistance to RIF and INH was assessed. Results In 767 pulmonary tuberculosis (PTB) patients, InnowaveDX showed significantly higher sensitivity than the Xpert MTB/RIF assay (Cepheid, USA) (74.97% versus 68.18%; p = 0.003, χ 2 = 8.664). This difference was particularly notable in culture-negative PTB cases (52.73% versus 41.29%; p = 0.001, χ 2 = 10.565). Both tests demonstrated high specificity in 286 non-TB patients. The overall consistency in RIF susceptibility prediction between InnowaveDX and the Xpert assay was 97.3% (505/519). InnowaveDX identified 83.05% (98/118) of INH-resistant cases as predicted by phenotypic drug susceptibility testing (pDST) and 95.45% (105/110) by another molecular method (MeltPro, Zeesan, China) for INH resistance detection on isolates. In addition, InnowaveDX showed a 99.35% consistency (154/155) with katG , inhA , and ahp C sequencing on sputum samples. The consistency rate for MDR-TB prediction between InnowaveDX and pDST was 93.25% (332/356). The accuracy of using RR to predict MDR-TB varied between 64.1 and 80.5%, depending on the reference method. Conclusion InnowaveDX is an easy, rapid, and sensitive molecular test for PTB diagnosis that can detect INH and RIF resistance within 3 h, facilitating MDR-TB diagnosis on the first day of hospital admission.